CA2321169C - Enzymes modifiees et leur utilisation pour la synthese peptidique - Google Patents
Enzymes modifiees et leur utilisation pour la synthese peptidique Download PDFInfo
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- CA2321169C CA2321169C CA2321169A CA2321169A CA2321169C CA 2321169 C CA2321169 C CA 2321169C CA 2321169 A CA2321169 A CA 2321169A CA 2321169 A CA2321169 A CA 2321169A CA 2321169 C CA2321169 C CA 2321169C
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- enzyme
- modified
- esterase
- amino acid
- cysteine
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- 235000019764 Soybean Meal Nutrition 0.000 description 1
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- 239000008351 acetate buffer Substances 0.000 description 1
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- 238000005917 acylation reaction Methods 0.000 description 1
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- 238000007098 aminolysis reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
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- 108010055059 beta-Mannosidase Proteins 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
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- 239000007853 buffer solution Substances 0.000 description 1
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
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- 239000012141 concentrate Substances 0.000 description 1
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- 238000006471 dimerization reaction Methods 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- SQNZJJAZBFDUTD-UHFFFAOYSA-N durene Chemical compound CC1=CC(C)=C(C)C=C1C SQNZJJAZBFDUTD-UHFFFAOYSA-N 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
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- 108010093305 exopolygalacturonase Proteins 0.000 description 1
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- 235000013922 glutamic acid Nutrition 0.000 description 1
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
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- 239000004615 ingredient Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000003367 kinetic assay Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
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- 230000007246 mechanism Effects 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 150000002742 methionines Chemical class 0.000 description 1
- ZAFLDFBNKJMEQR-UHFFFAOYSA-N methyl-oxo-[(2,3,4,5,6-pentafluorophenyl)methoxy]-sulfanylidene-$l^{6}-sulfane Chemical compound CS(=O)(=S)OCC1=C(F)C(F)=C(F)C(F)=C1F ZAFLDFBNKJMEQR-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- XDEPVFFKOVDUNO-UHFFFAOYSA-N pentafluorobenzyl bromide Chemical compound FC1=C(F)C(F)=C(CBr)C(F)=C1F XDEPVFFKOVDUNO-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229940085127 phytase Drugs 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 239000004456 rapeseed meal Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
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- 239000000523 sample Substances 0.000 description 1
- 235000016491 selenocysteine Nutrition 0.000 description 1
- ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 1
- 229940055619 selenocysteine Drugs 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000004455 soybean meal Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000012799 strong cation exchange Methods 0.000 description 1
- FRGKKTITADJNOE-UHFFFAOYSA-N sulfanyloxyethane Chemical compound CCOS FRGKKTITADJNOE-UHFFFAOYSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 108010074429 thiolsubtilisins Proteins 0.000 description 1
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
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- 235000013311 vegetables Nutrition 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/02—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length in solution
- C07K1/023—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length in solution using racemisation inhibiting agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06086—Dipeptides with the first amino acid being basic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06104—Dipeptides with the first amino acid being acidic
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
- C12N9/54—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea bacteria being Bacillus
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/8215—Microorganisms
- Y10S435/822—Microorganisms using bacteria or actinomycetales
- Y10S435/832—Bacillus
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/8215—Microorganisms
- Y10S435/822—Microorganisms using bacteria or actinomycetales
- Y10S435/832—Bacillus
- Y10S435/836—Bacillus licheniformis
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Engineering & Computer Science (AREA)
- Analytical Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Enzymes And Modification Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Detergent Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
La présente invention concerne des enzymes modifiées, un ou plusieurs restes d'acides aminés issus d'une enzyme étant remplacés par des restes de cystéine. Dans ces enzymes, certains des restes de cystéine au moins sont modifiés en remplaçant un hydrogène du thiol dans le reste de cystéine par une chaîne latérale thiolique pour former une enzyme modifiée, l'enzyme modifiée présentant une grande activité estérasique et une faible activité amidasique. L'invention concerne également un procédé permettant de produire ces enzymes modifiées. La présente invention concerne enfin un procédé d'utilisation des enzymes dans la synthèse peptidique.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7226598P | 1998-01-23 | 1998-01-23 | |
| US7235198P | 1998-01-23 | 1998-01-23 | |
| US60/072,351 | 1998-01-23 | ||
| US60/072,265 | 1998-01-23 | ||
| PCT/US1999/001413 WO1999037324A1 (fr) | 1998-01-23 | 1999-01-21 | Enzymes modifiees et leur utilisation pour la synthese peptidique |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2321169A1 CA2321169A1 (fr) | 1999-07-29 |
| CA2321169C true CA2321169C (fr) | 2011-08-02 |
Family
ID=26753173
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2321169A Expired - Fee Related CA2321169C (fr) | 1998-01-23 | 1999-01-21 | Enzymes modifiees et leur utilisation pour la synthese peptidique |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US6395532B1 (fr) |
| EP (1) | EP1047445B1 (fr) |
| JP (2) | JP2002500874A (fr) |
| KR (1) | KR20010040397A (fr) |
| AU (1) | AU739432C (fr) |
| CA (1) | CA2321169C (fr) |
| DK (1) | DK1047445T3 (fr) |
| NZ (1) | NZ506346A (fr) |
| WO (1) | WO1999037324A1 (fr) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6908757B1 (en) | 1998-03-26 | 2005-06-21 | The Procter & Gamble Company | Serine protease variants having amino acid deletions and substitutions |
| US6495136B1 (en) | 1998-03-26 | 2002-12-17 | The Procter & Gamble Company | Proteases having modified amino acid sequences conjugated to addition moieties |
| KR20010034697A (ko) | 1998-03-26 | 2001-04-25 | 데이비드 엠 모이어 | 아미노산 치환을 갖는 세린 프로테아제 변이체 |
| AU749383B2 (en) | 1998-07-02 | 2002-06-27 | Genencor International, Inc. | Chemically modified proteins with a carbohydrate moiety |
| AU772427B2 (en) * | 1998-11-10 | 2004-04-29 | Genencor International, Inc. | Chemically modified mutant serine hydrolases show improved catalytic activity and chiral selectivity |
| MXPA01010896A (es) * | 1999-04-28 | 2003-06-24 | Genencor Int | Antagonistas cataliticos especificamente dirigidos al objetivo y usos de los mismos. |
| US6627744B2 (en) | 1999-07-02 | 2003-09-30 | Genencor International, Inc. | Synthesis of glycodendrimer reagents |
| US6946128B1 (en) | 1999-07-22 | 2005-09-20 | The Procter & Gamble Company | Protease conjugates having sterically protected epitope regions |
| MXPA02000842A (es) | 1999-07-22 | 2002-07-30 | Procter & Gamble | Conjugados de proteasa que tienen sitios de corte protegidos estericamente. |
| BR0012660A (pt) | 1999-07-22 | 2002-04-09 | Procter & Gamble | Variante de protease tipo subtilisina; composição de limpeza; e composição de cuidado pessoal |
| CN1373802A (zh) | 1999-07-22 | 2002-10-09 | 宝洁公司 | 在特定表位区域具有氨基酸缺失和取代的枯草杆菌蛋白酶变体 |
| BR0012692A (pt) * | 1999-07-22 | 2002-04-09 | Procter & Gamble | Conjugado de protease, composição de limpeza e composição de tratamento pessoal |
| BR0316488A (pt) * | 2002-11-25 | 2005-10-11 | Zealand Pharma As | Métodos para modular uma comunicação de junção lacunar em uma população de células, e para tratar um paciente tendo ou sob risco de desenvolver uma condição patológica envolvendo comunicação de junção lacunar deficiente, uso de um peptìdeo, e, composição farmacêutica |
| US7087438B2 (en) * | 2004-07-26 | 2006-08-08 | Infineon Technologies Ag | Encapsulation of conductive lines of semiconductor devices |
| EP2596087B1 (fr) | 2010-07-22 | 2015-12-16 | Unilever PLC | Combinaisons de rhamnolipides et d'enzymes pour nettoyage amélioré |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58144105A (ja) * | 1982-02-12 | 1983-08-27 | Kurabo Ind Ltd | スケ−ル除去獣毛繊維の製法 |
| US5244791A (en) * | 1984-05-29 | 1993-09-14 | Genecor International, Inc. | Methods of ester hydrolysis |
| US5155033A (en) | 1989-01-06 | 1992-10-13 | Genencor, Inc. | Subtilisins modified at position 225 resulting in a shift in catalytic activity |
| US5037741A (en) * | 1986-08-18 | 1991-08-06 | The Coca Cola Company | Enzymatic method for the synthesis and separation of peptides |
| CN1056187C (zh) | 1988-02-11 | 2000-09-06 | 金克克国际有限公司 | 新的蛋白水解酶及其在洗涤剂中的应用 |
| DK97190D0 (da) | 1990-04-19 | 1990-04-19 | Novo Nordisk As | Oxidationsstabile detergentenzymer |
| US5629173A (en) * | 1990-08-09 | 1997-05-13 | Genentech, Inc. | Methods of use of serine protease variants having peptide ligase activity |
| EP0542931B1 (fr) * | 1990-08-09 | 1999-12-08 | Genentech, Inc. | Variantes de serine-proteases presentant une activite de ligase peptidique |
| US5316935A (en) | 1992-04-06 | 1994-05-31 | California Institute Of Technology | Subtilisin variants suitable for hydrolysis and synthesis in organic media |
| GB9416841D0 (en) * | 1994-08-19 | 1994-10-12 | Finnfeeds Int Ltd | An enzyme feed additive and animal feed including it |
| US5837516A (en) | 1995-03-03 | 1998-11-17 | Genentech, Inc. | Subtilisin variants capable of cleaving substrates containing basic residues |
-
1999
- 1999-01-21 US US09/234,957 patent/US6395532B1/en not_active Expired - Lifetime
- 1999-01-21 WO PCT/US1999/001413 patent/WO1999037324A1/fr not_active Ceased
- 1999-01-21 NZ NZ506346A patent/NZ506346A/xx not_active IP Right Cessation
- 1999-01-21 KR KR1020007008073A patent/KR20010040397A/ko not_active Withdrawn
- 1999-01-21 AU AU23371/99A patent/AU739432C/en not_active Ceased
- 1999-01-21 CA CA2321169A patent/CA2321169C/fr not_active Expired - Fee Related
- 1999-01-21 EP EP99903318.6A patent/EP1047445B1/fr not_active Expired - Lifetime
- 1999-01-21 JP JP2000528304A patent/JP2002500874A/ja active Pending
- 1999-01-21 DK DK99903318.6T patent/DK1047445T3/da active
-
2002
- 2002-02-13 US US10/075,895 patent/US6576454B2/en not_active Expired - Lifetime
-
2009
- 2009-09-14 JP JP2009211777A patent/JP2010029195A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US6395532B1 (en) | 2002-05-28 |
| JP2010029195A (ja) | 2010-02-12 |
| AU2337199A (en) | 1999-08-09 |
| EP1047445A1 (fr) | 2000-11-02 |
| NZ506346A (en) | 2003-06-30 |
| US6576454B2 (en) | 2003-06-10 |
| WO1999037324A1 (fr) | 1999-07-29 |
| AU739432C (en) | 2002-05-16 |
| AU739432B2 (en) | 2001-10-11 |
| DK1047445T3 (da) | 2013-11-11 |
| US20020137177A1 (en) | 2002-09-26 |
| CA2321169A1 (fr) | 1999-07-29 |
| EP1047445A4 (fr) | 2001-09-12 |
| KR20010040397A (ko) | 2001-05-15 |
| JP2002500874A (ja) | 2002-01-15 |
| EP1047445B1 (fr) | 2013-08-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20170123 |